asialo-gm1-ganglioside and Abortion--Spontaneous

Topics: Abortion, Spontaneous; Adjuvants, Immunologic; Animals; Female; Fetal Resorption; Fetus; G(M1) Ganglioside; Glycosphingolipids; Humans; Immunity, Innate; Interferon Inducers; Mice; Mice, Inbred CBA; Mice, Inbred DBA; Models, Biological; Pregnancy; Tumor Necrosis Factor-alpha

Topics: Abortion, Spontaneous; Animals; Drug Synergism; Endometrium; Female; G(M1) Ganglioside; Glycosphingolipids; Indomethacin; Interleukin-2; Killer Cells, Natural; Litter Size; Lymphocyte Activation; Mice; Placenta; Pregnancy; Pregnancy, Animal

Topics: Abortion, Spontaneous; Animals; Crosses, Genetic; Female; Fetal Death; Fetal Resorption; G(M1) Ganglioside; Glycosphingolipids; Humans; Immunization; Lymphocytes; Mice; Mice, Inbred Strains; Models, Biological; Muridae; Pregnancy; Research Design; Species Specificity; Tumor Necrosis Factor-alpha

Stress adversely affects pregnancy outcome and has been implicated as an abortogen in both animals and humans. However, the mechanisms whereby stress aborts are largely unknown. Alloimmunization can prevent stress-triggered abortion, and immunization is known to increase transforming growth factor-beta 2 (TGF-beta 2)-related suppressive activity.. To investigate these mechanisms, DBA/2J males were mated to CBA/J or C3H/HeJ females, and the pregnant females were exposed to ultrasonic sound stress for a period of 24 h between day 4.5 to 8.5 of pregnancy.. Ultrasonic stress significantly elevated the resorption rate with a peak effect on day 5.5 in the CBA/J females and on day 4.5 in the LPS-resistant C3H/HeJ females. The tumor necrosis factor-alpha (TNF-alpha) release from the decidua was also elevated and the TGF-beta 2-mediated suppressive activity was significantly decreased. The resorption rate only increased when the TNF-alpha/TGF-beta 2 ratio was increased compared to the control.. These data suggest that stress may inhibit protective suppressor mechanisms and promote secretion of abortogenic cytokines such as TNF-alpha. Possible mechanisms are discussed.

Topics: Abortion, Spontaneous; Animals; Decidua; Disease Models, Animal; Female; Fetal Resorption; G(M1) Ganglioside; Immunization; Isoantigens; Male; Mice; Mice, Inbred Strains; Noise; Pest Control; Pregnancy; Pregnancy Complications; Psychoneuroimmunology; Stress, Physiological; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha; Ultrasonics

Spontaneous resorption (abortion) that occurs at a high rate in DBA/2-mated CBA/J female mice is dependent upon asialoGM1+ natural effector-type cells, can be ameliorated by alloimmunization or administration of GM-CSF, and is augmented by in vivo injection of anti-CD8 antibody. The abortion rate was similarly augmented by administration of monoclonal anti-GM-CSF neutralizing antibody, but the GM-CSF physiologically active in preventing abortion during normal pregnancy did not appear to be derived from maternal CB8+ T cells putatively responding to antigens on the fetoplacental unit. Rather, depletion of CD8+ cells in vivo prevented GM-CSF from reducing the rate of resorptions. GM-CSF administration rapidly downregulates natural effector cells able to kill a trophoblast target cell line in vitro, and anti-CD8+ antibody boosts total splenic cytotoxic cell activity. Further, anti-CD8 completely abrogated the ability of GM-CSF to suppress anti-trophoblast killer cell activity. These cells are known to be asialoGM1+ and injection of anti-asialoGM1 reduced the abortion rate appropriately in mice that had received anti-CD8. These data suggest that GM-CSF acts indirectly to prevent abortion in DBA/2-mated CBA/J mice through a mechanism that requires CD8+ maternal T cells, and systemic regulation of the level of anti-trophoblast killer cell activity may determine the success or failure of pregnancy in this system.

Topics: Abortion, Spontaneous; Animals; Antibodies; CD8 Antigens; Cytotoxicity, Immunologic; Female; Fetal Resorption; G(M1) Ganglioside; Granulocyte-Macrophage Colony-Stimulating Factor; Immune Tolerance; Killer Cells, Natural; Male; Mice; Mice, Inbred CBA; Mice, Inbred DBA; Pregnancy; T-Lymphocyte Subsets; Trophoblasts

Effector cells associated with an aborting fetus appear to be both thymus derived (T) and natural killer (NK) cells. In order to test the hypothesis that NK cells are a major effector mediating early spontaneous abortion (less than day 8-10), CBA female mice mated by DBA/2 males were treated with either polyinosinic/cytidylic acid (poly I:C) to boost NK activity, or rabbit anti-asialo GM1 (RaASGM1) to decrease NK activity. The results of the NK assays of the spleens of treated mice confirmed that the reagents had the expected effect on NK activity and an inspection of the uteri indicated a significant increase in aborted embryos after poly I:C and a marked decrease in spontaneous abortions after RaASGM1 treatment. Therefore, spontaneous abortions may be mediated in part by the cytotoxic activity of unregulated NK cells.

Topics: Abortion, Spontaneous; Animals; Female; G(M1) Ganglioside; Glycosphingolipids; Killer Cells, Natural; Male; Mice; Mice, Inbred Strains; Poly I-C; Pregnancy